MICROBIAL SUPERANTIGENS AND AUTOIMMUNITY

两种自身免疫性疾病动物模型致病T细胞的研究 在人类中自发产生的自身免疫性疾病已经证明 选择性使用特定T细胞受体(TCR)β链变量(V) 基因。最近对一类微生物产品的表征， 被称为超抗原(SA)，是基于TCR的T细胞有丝分裂原 Vbeta基因的使用，表明微生物SA可能在 感染和自身免疫。虽然临床上公认的证候 可归因于SA的特征通常是休克和免疫抑制， 我们的实验室最近证明了它的免疫刺激作用。 人体免疫系统体液臂上的一些微生物SA。这个 这项提案的目标是分析三个拟议的机制，通过这些机制 微生物SA可能起到刺激免疫系统的作用，进而， 可能会导致自身免疫。具体地说，我们建议调查：1) 微生物SA促进T细胞依赖性B细胞的机制 激活；2)直接SA传递给B细胞的激活信号 结合；3)微生物SA激活正常静止状态的潜力 自身反应性T细胞；4)微生物SA和微生物SA反应性的作用 自身免疫动物模型中的T细胞。

Studies of pathogenic T cells in both animal models of autoimmune disease and spontaneously arising autoimmune disorders in man have demonstrated the selective use of particular T cell receptor (TCR) beta chain variable (V) genes. The recent characterization of a class of microbial products, termed superantigens (SA), which are mitogenic for T cells based on TCR Vbeta gene usage, suggests that microbial SA may provide the link between infection and autoimmunity. While clinically recognized syndromes attributable to SA are often characterized by shock and immunosuppression, our laboratory has recently demonstrated the immunostimulatory effects of some microbial SA on the humoral arm of the human immune system. The objective of this proposal is to analyze three proposed mechanisms by which microbial SA may function to stimulate the immune system and, by extension, may lead to autoimmunity. Specifically, we propose to investigate: 1) the mechanisms by which microbial SA promote T cell-dependent B cell activation; 2) the activation signal delivered to B cells by direct SA binding; 3) the potential for microbial SA to activate normally quiescent autoreactive T cells; 4) the role of microbial SA and microbial SA-reactive T cells in animal models of autoimmunity.